CompTox Webinar - PFAS mixtures: Maternal and neonatal effects of combined exposure to multiple PFAS

Multiple PFAS are commonly, if not ubiquitously, detected in human and environmental samples. Many health-based agencies are implementing cumulative PFAS assessment and regulatory approaches; however, the literature generally lacks joint exposure studies that incorporate mixture modeling to investigate the nature of PFAS mixture effects.  We have conducted three in vivo developmental toxicity studies of PFAS mixtures including a 2-PFAS mixture (perfluorooctanoate (PFOA) + perfluorooctanesulfonate (PFOS)), a 3-PFAS mixture (hexafluoropropylene oxide-dimer acid (HFPO-DA or ‘GenX chemicals’) + Nafion byproduct 2 (NBP2) + PFOS), and a 6-PFAS mixture (perfluoromethoxy-2-acetic acid (PFMOAA) + HFPO-DA + PFOA + perfluorohexanesulfonate (PFHxS) + NBP2 + PFOS).  For all individual compounds and mixtures, we exposed Sprague-Dawley rat dams to a range of doses via oral gavage from gestation day 8 (GD8) to postnatal day 2 (PND2) and evaluated maternal and neonatal endpoints.  Dose-response data from individual PFAS studies were modeled to obtain non-linear regression parameters and established mixture models were used to evaluate observed mixture effects including equations for dose addition and response addition and a relative potency factor approach.  In the 2- and 3-PFAS mixture studies endpoints were well-predicted by dose addition, which produced equivalent or better statistical fits of the observed mixture data than response addition.  For the 6-PFAS mixture study, the observed data indicated slightly greater mixture potency (~2-fold) than predicted by dose addition.  Overall, combined exposure to mixtures of PFAS produced cumulative effects on multiple maternal and neonatal endpoints and these effects were generally well predicted by dose addition-based approaches.  The views expressed in this abstract are those of the author(s) and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.             

Impact/Purpose

This is an overview abstract and slide deck for an invited presentation to the EPA Computational Toxicology Communities of Practice webinar series.  The focus of the presentation is on the mixture-based effects of exposure to multiple PFAS.  Our lab group has conducted and published some of the only in vivo experiments to test the nature of PFAS mixture effects.  This presentation will cover previously published and on-going PFAS mixture studies from our lab. The studies described here are some of the only mammalian in vivo mixture toxicity studies of PFAS that incorporate mixture modeling and analyses to characterize the type of mixture effects and the accuracy of predictions using well-established approaches.  The results directly support the proposed approaches by the Office of Water, as well as state and international health-based agencies that have adopted mixture-based risk assessment and regulatory approaches for exposure to multiple PFAS.

Citation

Conley, J. CompTox Webinar - PFAS mixtures: Maternal and neonatal effects of combined exposure to multiple PFAS. US EPA Computational Toxicology Communities of Practice Monthly Webinar, Virtual, NC, March 27, 2025.